In the deep lung where gas exchange occurs, the alveoli are lined with a liquid layer containing pulmonary surfactant (PS) which lowers the surface tension by alignment at the air-water interface. The major surface-active components are phosphatidylcholines (PC), in which as much as 30% of the fatty acids are unsaturated, presenting potential reaction sites for inhaled oxidant air pollutants. While inhalation of such pollutants as 03 is known to cause a change in the chemical composition of PS, it is not own if this is due to a direct chemical reaction between them. Furthermore, the relationship between the oxidant-PS interaction and the inflammatory response induced 24-48 hours post-exposure is not clear. The proposed research and addresses these two problems using a unique combination of in vitro and in vivo studies, the latter in collaboration with the Air Pollution Health Effects Laboratory at the University of California, Irvine. Specific questions to be answered by the in vifto work include the following: (1) Which of the monounsaturated and polyunsaturated PC found in PS form relatively stable secondary ozonides? (2) How do secondary ozonides react at the air-water interface? (3) What are the products of reaction of the PC in PS with 03, N02 d N205 when the lipid is at the air-water interface? A combination of proven analytical methodologies including HPLC, GC-MS, FAB-MS, NMR, UV and FTIR, will be used to separate and identify the products. Questions to be addressed through in vivo studies include: (1) Are ferrets an appropriate animal model for oxidant inhalation? (2) Can reaction products characteristic of the PS-oxidant reaction be detected in ferrets exposed to the air pollutants in vivo? Changes in breathing pattern, minute ventilation and metabolic rate will be followed in ferrets exposed to 03, N02 and their combination (which forms N 2050) during the exposures, and a search made for the induction of an inflammatory response as indicated by respiratory tract injury and changes in Ps composition 24-48 hours post-exposure. Finally, a search will be made for the PS-oxidant reaction products expected from the results of the in vitro work.